Experience-dependent plasticity in the developing brain

Hebb’s postulate

Hebb's postulate is often summarized with the phrase "Fire together, wire together." This postulate suggests that the coordinated electrical activity of a presynaptic terminal and a postsynaptic neuron strengthens the synaptic connection between them. In other words, when the two neurons are active at the same time, their connection becomes stronger. Conversely, if their activity is uncorrelated, the connection is gradually weakened and may eventually be eliminated.

Phenomena in brain development

• Behaviors not initially present in newborns emerge and are shaped by experience throughout early life.

• There is a superior capacity for acquiring complex skills and cognitive abilities during early life.

• The brain continues to grow after birth, roughly in parallel with the emergence and acquisition of increasingly complex behaviors and the addition of pre- and post-synaptic processes.

Brain Changes in Postnatal Life

• The brain undergoes significant changes during postnatal life.

• It consists of two main phases:

  1. Construction Phase: This phase involves post-natal growth of dendrites, axons, and synapses, leading to the formation of neural connections.

  2. Elimination Phase: In this phase, the brain continues to develop by eliminating and refining synapses, resulting in the continued elaboration of the remaining connections.

Critical Periods

• Critical periods refer to the specific times during development when experience and neural activity have the greatest impact on the acquisition or skilled execution of a particular behavior.

• Examples of critical periods include:

  • Parental imprinting in hatchling birds, where certain experiences during a restricted time influence attachment to parental figures.

  • Critical periods for sensorimotor skills and complex behaviors, which allow for extensive environmentally acquired experiences.

  • Communication skills in songbirds, where the ability to learn and produce songs is time-sensitive.

  • Language acquisition in humans, where early childhood is a critical period for the development of linguistic skills.

Spontaneous Activity in Retinogeniculocortical Pathway

• Spontaneous activity establishes rudimentary patterns of connectivity in the retinogeniculocortical pathway.

• Local oscillations or "waves" of subthreshold activity are essential for shaping circuit networks, preparing them for optimal experience-driven activity.

• Spontaneous activity, such as retinal waves, occurs before birth and before eye opening.

• Each retina independently generates a pattern of waves of electrical activity that moves across large populations of retinal cells in an orderly fashion.

• These waves are initiated in local retinal cells (amacrine cells), leading to action potential firing by ganglion cells, which is then relayed to the lateral geniculate nucleus (LGN) and subsequently to primary visual cortex (V1).

• The activity in each eye is coherent but asynchronous between the two eyes, leading to competitive interactions between the two eyes during development.

Ocular Dominance Columns in V1

• Ocular dominance columns in primary visual cortex (V1) result from the competitive interaction between the two eyes during development.

• Afferents (input connections) driven by one eye segregate from those of the other eye, leading to the formation of ocular dominance columns.

• Ocular dominance columns are an alternating series of eye-specific domains found in cortical layer 4 of V1.

• Cells in layer 4 of V1 respond strongly or exclusively to stimulation of either the left or right eye.

• Neurons in layers above and below layer 4 integrate inputs from both the left and right eyes and respond to visual stimuli seen by both eyes, contributing to binocular vision and depth perception.

Ocular Dominance Groups in Visual Cortex

• Visual cortical neurons are divided into seven ocular dominance groups based on their degree of response to either the contralateral or ipsilateral eye.

• Group 1 cells are driven only by the contralateral eye.

• Group 7 cells are driven entirely by the ipsilateral eye.

• Group 4 cells respond equally well to either eye.

• In a normal adult cat, most cells are activated to some degree by both eyes, and this distribution of ocular dominance can be altered by visual experience

Effects of Early Visual Deprivation

• When one eye of a kitten is sutured closed early in life and then opened at 2.5 months, the kitten matures normally to 38 months.

• However, very few cortical cells can be driven from the deprived (previously sutured) eye.

• Recordings from the retina and lateral geniculate nucleus (LGN) remain normal, but the deprived eye becomes functionally disconnected from the visual cortex.

• The kitten is behaviorally blind in the deprived eye, a condition known as amblyopia or "cortical blindness," which is typically permanent.

Effects of Adult Visual Deprivation

• The same manipulation of closing one eye performed in adulthood has no effect on the responses of cells in the mature visual cortex.

• Ocular dominance distribution and visual behavior through the reopened eye are indistinguishable from normal.

• The crucial period for determining how the visual cortex is wired with respect to eye dominance occurs between the opening of the kitten's eyes and 1 year of age, influenced by visual experience during this time.

Critical Period for Ocular Dominance

• At the height of the critical period, even a short period of 3-4 days of eye closure can profoundly alter the ocular dominance profile in the primary visual cortex (V1).

• After this critical period, deprivation or manipulation has little or no permanent effect on the organization of ocular dominance in V1.

Ocular Dominance Column Pattern

• In monkeys, the stripe-like pattern of geniculocortical axon terminals in layer 4 that defines ocular dominance columns is already present at birth.

• This pattern reflects the functional segregation of inputs from the two eyes.

• It occurs even in the absence of meaningful visual experience and consists of alternating stripes of roughly equal width.

Effects of Early Visual Deprivation on Ocular Dominance Columns

• Animals deprived from birth of vision in one eye develop abnormal patterns of ocular dominance stripes in primary visual cortex (V1).

• These altered patterns of activity are caused by deprivation, where stripes related to the open eye become substantially wider.

• Conversely, stripes representing the deprived eye become correspondingly diminished.

• Inputs from the active (open) eye take over some, but not all, of the territory that formerly belonged to the inactive (closed) eye, reflecting competitive interaction for post-synaptic space in V1.

Effects of Monocular Deprivation on LGN Axons

• Monocular deprivation can impact the arborizations of lateral geniculate nucleus (LGN) axons in the visual cortex.

• This refers to the changes in the branching and connectivity of axons that transmit visual information from the LGN to the visual cortex.

Importance of Studying Effects on LGN Axons

• This research is important for several reasons:

• It can aid in the diagnosis and early treatment of amblyopia (lazy eye), a condition often associated with abnormal visual development.

• Early intervention is only possible if amblyopia is diagnosed in its early stages.

• Unfortunately, early diagnoses are not always available before the critical period for visual development has closed.

• Individuals who experience uncorrected abnormal ocular competition early in life may suffer permanent visual impairment, underscoring the significance of understanding the effects on LGN axons.

Potential Interventions for Monocular Deprivation

• Rats that experienced monocular deprivation from the critical period onset through adulthood were divided into two groups.

• Half were placed in a completely light-free environment (termed "dark exposed") for 10 days.

• The other half remained in standard illumination conditions.

• Both groups were then tested on a visual acuity task to evaluate potential interventions.

Mechanisms of Dark Exposure

• The mechanisms by which dark exposure reactivates cortical synaptic plasticity and permits reactivation of visual capacity remain uncertain.

• Dark exposure is known to increase the density of spines on visual cortical neuron dendrites.

• The research indicates that the adult visual cortex retains measurable capacity for plasticity, which can improve visual function if specific conditions are established.

• These conditions may include dark exposure and repeated training.

Dark Exposure for Visual Plasticity

• Dark exposure refers to a period in which individuals are placed in a completely light-free environment.

• This intervention can potentially reactivate cortical synaptic plasticity and rekindle visual capacity.

• It is one of the strategies used to enhance plasticity in the adult visual cortex, which may lead to improved visual function.

• Additionally, repeated training is another approach that may help harness the plasticity of the adult visual cortex for visual improvement.

Strabismus

• Strabismus is a condition where the eyes do not align properly and do not point in the same direction.

• In humans, amblyopia (lazy eye) is most often the result of strabismus.

• There are two main types of strabismus:

  • Convergent strabismus, known as esotropia or "crossed eyes," where the eyes turn inward.

  • Divergent strabismus, known as exotropia or "wall eyes," where the eyes turn outward.

• Both types of alignment errors produce double vision.

Prevalence of Strabismus

• Strabismus is a very common condition, affecting approximately 5% of children.

• It is characterized by the misalignment of the eyes, leading to visual and perceptual challenges.

• Early detection and intervention are crucial for the treatment of strabismus and any related conditions.

Competitive Advantage of Aligned Eye

• In individuals with strabismus, inputs to the lateral geniculate nucleus (LGN) from the optimally aligned eye are competitively advantaged.

• This means that the eye that is correctly aligned with the target receives more territory in the primary visual cortex (V1).

• The eye that is suppressed or misaligned may eventually have very low acuity, which can render an individual effectively blind in that eye.

Ocular Asynchrony

• Ocular asynchrony refers to the condition in which the input from both eyes remains active but is highly asynchronous.

• In this state, the ocular dominance pattern in layer 4 of the primary visual cortex (V1) is sharper than normal.

• Cells in all layers of V1 become exclusively driven by one eye or the other due to this asynchrony.

• Ocular asynchrony prevents binocular interactions in other layers of V1.

Manipulating Competition

• Manipulating competition involves testing the role of correlated activity in driving the competitive postnatal rearrangement of cortical connections.

• In this context, activity levels in each eye remain the same, but the correlations between the two eyes are intentionally altered.

• One method of manipulation is to cut one of the extraocular muscles in one eye during the critical period, resulting in strabismus (misalignment of the eyes).

• This misalignment leads to a situation where objects in the same location in visual space no longer stimulate corresponding points on the two retinas at the same time.

• As a consequence, the differences in visually evoked patterns of activity between the two eyes become far greater than normal.

• Notably, unlike monocular deprivation, the overall amount of activity in each eye remains roughly the same.

Tuning Properties of Neurons in Visual Cortex

• Neurons in the lateral geniculate nucleus (LGN) exhibit a similar arrangement as in the retina. They have center-surround receptive fields and are selective for increases or decreases in luminance, meaning they respond to changes in brightness.

• In contrast, cells in the primary visual cortex (V1) respond selectively to oriented bars and edges in the visual field. These cells have "preferred" orientations to which they are most responsive.

Binocular Competition in the Critical Period

• During the critical period, binocular competition aligns orientation tuning in binocularly innervated cortical neurons.

• Prior to eye opening, there is little or no correlation between the relatively broad orientation sensitivities in visual cortex neurons driven by both eyes.

• There is a fairly low maximal response to preferred orientations, and the orientations are dissimilar between the two eyes.

• At the start of the critical period, the magnitude of responses increases in both eyes, but the orientation preference remains dissimilar.

• Increased correlation of visually evoked stimuli leads to the matching of orientation tuning of the right and left eye inputs to single cortical binocularly driven neurons.

Effect of Closing One Eye during the Critical Period

• If one eye is closed during the critical period, the matching of orientation tuning of binocular inputs does not occur.

• This alignment of orientation tuning cannot be restored once the closed eye is opened, emphasizing the importance of normal visual input during the critical period for proper development of binocular vision and orientation tuning.

Cataracts

• Cataracts are eye conditions that render the lens or cornea opaque, obstructing vision.

• Functionally, cataracts are equivalent to monocular deprivation in experimental animals, leading to visual deficits.

• If left untreated in children, cataracts can result in irreversible damage to visual acuity in the deprived eye.

• Early treatment, before 4 months of age, can largely avoid severe deficits.

• Even in cases of bilateral cataracts, there may be less dramatic deficits if treatment is delayed, but the critical period for normal vision remains important.

Effects of Cataracts on Vision

• 
  Cataracts can have effects on vision similar to Hubel and Wiesel's binocular deprivation in experimental animals.

• Unequal competition during the critical period for normal vision is much more deleterious than the complete disruption of visual input.

• Individuals who are monocularly deprived of vision after the critical period has ended are much less compromised compared to those with cataracts or early-life deprivation.

Language Development in Deaf Babies

• Deaf babies, when exposed to sign language at an early age, engage in manual babbling, using their hands to communicate.

• This manual babbling is analogous to oral babbling seen in hearing babies around 7 months of age.

• Regardless of the modality (oral or manual), early experiences shape language behavior in infants.

Critical Period for Language Learning

• There is a critical period for language learning, during which individuals are most adept at acquiring new languages.

• The ability to learn a second language with native-like pronunciation and fluent grammar typically declines with age.

Age-Related Decline in Language Learning

• As individuals age, there is a decline in fluency and the ability to speak a non-native language without an accent.

• Children can usually learn a second language without an accent and with fluent grammar until about age 7-8.

• After this age, language learning performance gradually declines, regardless of the extent of practice or exposure.

Synapse Addition and Elimination in Cortex

• The number of synapses throughout the cortex follows a dynamic pattern:

  • Increases during prenatal and a limited period of postnatal life.

  • Declines during a protracted period that includes much of adolescence.

  • Reaches a steady state in early adulthood.

• Critical periods in cortical development may be mediated by:

  • Local growth of neural elements.

  • Elimination of some synapses.

  • Selective growth and stabilization of other synapses.

• This indicates a cellular basis for activity-dependent plasticity and critical period phenomena throughout the cerebral cortex.

Gray Matter Volume Changes

• In humans, gray matter volume follows a pattern:

  • It increases during early development.

  • It decreases during later stages of development.

• This pattern of increasing and then decreasing gray matter volume parallels critical periods in human brain development.

White Matter Volume Changes

• In contrast to gray matter, white matter volume increases throughout early childhood and adolescence.

• This signifies a prolonged process of experience-driven construction of cortical circuits in the brain.

Impact on Brain Disorders

• The altered patterns of gray matter and white matter volume changes can have implications for several neurological and psychological disorders.

• Understanding these changes can shed light on the development of brain circuits and may help in understanding and addressing disorders associated with brain structure and function.

Gray Matter Growth and Decline

• Gray matter, which contains the location of synapses in the cerebral cortex, exhibits a specific pattern of growth and decline.

• It grows throughout the cortex during early life.

• It then declines slightly over a protracted period of late childhood and early adolescence.

Disorders and Altered Gray Matter

• Gray matter alterations have been observed in several neurological and psychological disorders, including autism, schizophrenia, and ADHD.

• Understanding these changes in gray matter can provide insights into the development and function of the cerebral cortex and how it is affected in these disorders.

ADHD and Gray Matter Volume

• Attention Deficit Hyperactivity Disorder (ADHD) is a behavioral disorder that is accompanied by alterations in the addition of gray matter volume in the brain.

• In children with ADHD, gray matter volume increases at a slower rate compared to typically developing children.

• Although the rate of decline in gray matter volume is equivalent, the net result is lower gray matter volume in adults with ADHD.

• These structural differences in the brain may contribute to the cognitive and behavioral symptoms associated with ADHD